Estrogen's Influence on Neuroinflammation May Explain Sex Differences in Environmental Illness.

Previously we noted that the estrogen signalling may influence expression of Nrf2 enzymes. A new study provides support that estrogen may provide some protection against LPS exposure effects. It has been noted by a number of researchers the sexual dimorphism that occurs with environmental conditions including CFS, FM and MCS and this relationship could provide a mechanism for the significantly higher prevalence of some EI conditions in women especially as they get older.

"these studies identify a dramatic cytokine- and chemokine-mediated neuroinflammatory response that is regulated through ERalpha- and ERbeta-mediated ligand-dependent and ligand-independent mechanisms"

Read more: CiteULike: Production of Proinflammatory Cytokines and Chemokines During Neuroinflammation: Novel Roles for Estrogen Receptors alpha and beta:

Supplemental Resource: Yao, Y., Brodie, A. M., Davidson, N. E., Kensler, T. W., and Zhou, Q. (2010). Inhibition of estrogen signaling activates the nrf2 pathway in breast cancer. Breast cancer research and treatment. http://www.citeulike.org/user/HEIRS/article/7493023?show_msg=already_posted

Female Hormones May Contribute to Sexual Dimorphism in TMJ~!

Comment: I suspect this is going to has implications on other pain conditions as well, especially those under the environmental illness umbrella like CFS and fibromyalgia....

"hippocampal TRPV1 can modulate central pain processing and estradiol may contribute to the sexual dimorphism of TMD pain sensitivity through upregulation of TRPV1 expression in the hippocampus"

Link:CiteULike: 17-beta-Estradiol Enhanced Allodynia of Inflammatory Temporomandibular Joint through Upregulation of Hippocampal TRPV1 in Ovariectomized Rats:

Ammonia Enzymes, Immune Cells & X-Linked Mutations In Autoimmunity and Disease

Background: We have suggested that environmental illnesses may involve the loss of suppression of regulatory T cells and that several different proteins may be involved which changes the dynamics or "immunological footprint" of these conditions in each individual. Previously we mentioned how high ammonia levels may account for some of the symptoms associated with multiple chemical sensitivity. We also noted recently how alterations in ornithine enzymes may effect ammonia levels and the Nrf2 gene regulator has some control over its expression. The following article discusses findings related to how a mutation in ornithine transcarbamalase may influence the immune system and play a role in autoimmune type disease. Interestingly, the author points out the condition is X-linked which might account for higher number of females presenting with them because males usually die in utero and do not live but a few days after birth. There is usually a large sexual dimorphism in the prevalence of many environmental diseases. As Li explains, there may be a number of factors that contribute to autoimmune disease which may include estrogenic production as well as, vulnerable phenotypes may be more susceptible to metals exposure which may accelerate some individuals to reactive phenotypes. (Li)

The author writes, "Antigen expression in the thymus leads to the deletion of self-reactive T cells and generation of regulatory lymphocytes, including regulatory T cells(Treg) and NKT cells. We show an Ornithine transcarbamylase(OTC) mutation causes ineffective presentation of self antigens in the thymus. As such, deletion of self reactive T cells is compromised and production of Treg and NKT cells is reduced in the OTC mutant mice. More importantly the heterozygous mice have increased susceptibility to autoimmune diseases, including the generation of autoantibodies and more severe EAE." Further, "OTC mutant mice, the production of Treg in the thymus is reduced, which is correlated with the impaired antigen presentation due to hyperammonemia."


Comment: This article is a good representation of why only qualified medical professionals that understand the multitude of genetic conditions and environmental conditions that activate them should be treating them. There is no evidence thus far, that a "therapeutic recipe" is effective at treating all of them.


Chang, X. (2006). X linked foxp3 & otc in immune tolerance and autoimmunity. Ohio State University. http://www.citeulike.org/user/HEIRS/article/6650098
Li, J., Stein, T. D., and Johnson, J. A. (2004). Genetic dissection of systemic autoimmune disease in nrf2 deficient mice. Physiological Genomics.
http://www.citeulike.org/user/HEIRS/article/6604948

Estrogen Link In Male Aggression Sheds New Light On Sex-specific Behaviors

Estrogen Link In Male Aggression Sheds New Light On Sex-specific Behaviors